Panaji Sept 25: A study of only two Goan villages, Mandur and St Cruz, has revealed a prevalence of 2.9 per cent cases of dementia among people over the age of sixty. The study was conducted by Dr Amit Dias, secretary of the Dementia Society of Goa (DSG). In the past two years, the DSG has realised that degenerative diseases like Alzheimers disease do exist in Goa contrary to the belief of some people.The above information was given by the DSG president, Dr C J Vas, in a press release on the commencement of the National Dementia Awareness Week beginning on September 20. Dr Vas states that there are around 1 lakh people over the age of 60 in Goa and DSG believes there are at least 3000 people with dementia in the state. Though Goa enjoys better health services than most other states of the country, many patients travel to neighbouring cities for medical care. Facilities for diagnosis and management of the demented are meagre in Goa, but now have been initiated.

Dr Vas states that though homes have sprung up for the aged with the means but there is still a shortage of caring people. There is no home or respite centre for the demented anywhere in India but three day-care centres have been established in Kerala.

Besides Alzheimers disease, Goa also has other dementias like Lewy body, vascular, mixed, picks, CJD, progressive supranuclear palsy, alcohol induced and the like. Dr Vas states that three CJD cases have been reported. The first Goan patient investigated in Mumbai had classical manifestations of CJD and the autopsy confirmed it. Diagnostic activity in Goa has been hampered by the absence of standardised psychological instruments such as the MMSE, the Hindi MMSE, ADAS-cog, the CAMDEX and the like in Konkani. A beginning has now been made with a Konkani version of the MMSE and Dr Vas hopes others will follow if time and funds permit.

A qualitative study on ageing and mental health in Goa confirmed that family members were more often the main carers of the old but many elders lived alone and were subjected to abuse and neglect. They were often cheated of their meagre financial resources and property and had no legal protection. Dr Vas states that attempts are being made to remedy this lacuna.

The Dementia Society in Goa, founded in 2002, aims to have full-fledged home for those affected by Alzheimers in a 400-year old house gifted to the DSG by the Gonsalves family of Brittona. The DSG hopes that with the promised support and funds, a respite home and day care centre will be set up followed by the development of structured training for dementia-care workers and improvement in the facilities available for patients.

The society has also completed the Dementia - Home Care Project on a pilot basis in Bardez and Tiswadi and this has shown encouraging results. The project was supported by the World Health Organisation and aimed at empowering the carers. It could become the model for dementia services throughout the country, Dr Vas states.

http://www.navhindtimes.com/stories.php?part=news&Story_ID=09267

With the aged population of Goa growing rapidly, dementia has been a causeof concern. Goa has around 1 lakh people aged above 60, and the sixepidemiological studies have reported that the prevalence of dementia andAlzheimer's in India, ranged between 0 and 3.5% in the post-imaging era. Apilot study early last year by Dr. Amit Dias in Mandur, Goa, revealed aprevalence of 2.9% (around 3000), contrary to the belief of some. Otherdementia's like Lewy body, vascular, mixed, Picks, CJD, progressivesupranuclear palsy, alcohol induced and normal pressure hydrocephalus, havealso been noticed in Goa, says Dr. C.J. Vas of the Goa Medical College. Hestated that there was no Home or Respite Centre for the demented anywhere inIndia, though three day-care centres have been established in Kerala.

http://www.goanet.org/pipermail/goanet/2003-September/005423.html

Creutzfeldt-Jacob Disease(CJD) : Report of 10Cases from North IndiaI read with interest the article on Creutz-JacobDisease (CJD) : Report of 10 cases from NorthIndia.1 As the authors have remarked, CJD is beingincreasingly reported from various regions in India.CJD Registry at NIMHANS initiated by Shankar andSatish Chandra2 is a step in the right direction toknow about the prevalence of CJD in India.Singhal and Dastur,3 described 7 patients fromWestern India way back in 1983. There was autopsyconfirmation in 4 patients and attention was drawn tothe fact that 2 of the 7 patients were vegetarian. Theyalso documented the earlier reports of CJD from Indiain their article for historical purposes.References1. Mehndiratta MM, Bajaj BK, Gupta M et al : Creutzfeldt-Jacobdisease : Report of 10 cases from North India. Neurol India2001; 49 : 338-341.2. Shankar SK, Satish Chandra P : Creutzfeldt-Jacob disease Cases in India in 30 years (1968-1997). CJD RegistryNIMHANS, Bangalore, India.3. Singhal BS, Dastur DK : Creutzfeldt Jacob Disease inWestern India. Observation in 7 patients.Neuroepidemiology 1983; 2 : 92-100.B.S. SinghalDepartment of Neurology, Bombay Hospital Institute ofMedical Sciences, 12, Marine Lines, Mumbai - 400020, India.Authors ReplyI thank Dr. Singhal for showing interest in our article.I am aware of the study reported by Singhal et al in1983. I think incidence of CJD may be much morethan being reported. Many of the cases of CJD areprobably being underdiagnosed or misdiagnosed.Many of the patients may not report to the hospitalbecause of rapidly progressive course and deathoccuring within few weeks to months and cause ofdeath may get a dfferent label.M.M. Mehndiratta113 Neurology India, 50, March 2002MATTER ARISING

Over 40,000 deaths due to rabies are reported annually worldwide andeach year seven to eight million people receive antirabies vaccinetreatment following dog bites. Dog rabies poses a significant publichealth problem in Asia, as 85% of the human deaths due to rabiesreported worldwide and 80% of the vaccine doses applied indeveloping countries come from this part of the world.In many Asian countries such as Bangladesh, India, Nepal and Pakistan,sheep-brain based Semple vaccine 15 is the only vaccine available freeof cost. It represents 50 to 95% of all vaccine doses used for rabiespost-exposure treatment, depending upon the country. A completetreatment consists of 10 subcutaneous daily injectionsof 2 to 5 ml (depending mainly on patient size and nature of theexposure) plus booster doses; that is a total of 25 to 50 ml of the 5 %sheep brain suspension injected over a 10-day period.According to the literature, the reported rate of neuroparalyticcomplications following the use of this vaccine varies from 1:600 to1:1575 administrations, and 20-25% of these lead to death. The exactincidence of neuroparalytic complications throughout India or othercountries in the area is not known. However, in the State ofKarnataka, India, 112 cases of neuroparalytic accidents were admitted inthe past 20 years following Semple vaccine administration. In contrast,the newly developed cell culture or embryonating egg vaccines areeffective and safe, with lower and less severe complication rates.In many Asian countries, Semple type vaccine has been used for the past90 years. In India forty million ml of this vaccine are produced in thiscountry to treat at least 500 000 persons each year. In Pakistan 450 000and in Bangladesh 60 000 people receive Semple type vaccine afterpossible exposure to rabies. There is a theoretical risk of TSEtransmission to humans through parenteral administration ofthese products. Although there is to date no evidence of suchoccurrences in human medicine, recent events in the TSE field havedemonstrated that an animal TSE agent could affect human beings.The situation is very similar regarding rabies vaccines for animal use.For example various Indian veterinary vaccine institutes prepare 100million ml of Semple vaccine for use in both rabies pre-andpost-exposure prophylaxis in dogs and food production animals each year.Scrapie could be theoretically transmitted to animal vaccine recipients,especially ruminants, through sheep-brain based vaccines such asSemple type vaccine. This could happen because scrapie infectivity, ifpresent, would not be inactivated by the manufacturing process. In thisconnection, a recent 15 Ãx-propiolactone inactivated or phenolizedantirabies vaccine containing 5% suspension of sheep brain infected witha fixed strain of rabies virus.

WHO/CDS/CSR/APH/2000.2

34 WHO Consultation on Public Health and Animal TSEsEpidemiology, Risk and Research Requirements

publication strongly suggests that scrapie was transmitted to sheep andgoats through the administration of a veterinary vaccine whose method ofpreparation is similar to the Semple type vaccine. In addition, variousAsian countries have begun to use animal tissues as feed supplement forintensive sheep and dairy cattle production. This introduces anadditional, though still theoretical, possibility that scrapie, or evenBSE, could spread among the sheep population and enter the sheep flocksthat are used as a source of rabies vaccine production for human oranimal use. In areas where the status of animal TSE is not welldocumented, this risk cannot be totally ruled out, though it may beremote, as there is no test available at present to detectpre-clinical cases of prion disease in sheep.

snip...

Recommendation 25

Human vaccines prepared from whole ruminant brains may carry the risk oftransmission of animal TSE agents, because the inactivation processesusually applied to these products do not inactivate TSE agents. Inparticular, considering the recent emergence of vCJD in humans relatedto BSE in cattle, the consultation recommends that the use of thesevaccines should be avoided if suitable alternatives can be madeavailable. The Consultation strongly supported the recommendation madeby WHO Expert Committee on Rabies, which states:

"The (Expert) Committee reiterated, as stated in its 1983 report, itssupport for the trend to limit or abandon completely - whereeconomically and technically possible - the production ofencephalitogenic brain-tissue vaccines, and strongly advocated theproduction and use of inactivated cell-culture rabies vaccines in bothdeveloped and developing countries."

Recommendation 26

The use of veterinary vaccines prepared from whole ruminant brains, foruse in ruminants, should be avoided unless the process ensures TSEinactivation and/or removal, or the source animals have beendemonstrated to be free of any TSE.

55III.3. IATROGENIC TRANSMISSIONIatrogenic transmission of BSE has not been reported, or even suspected,in cattle but there are some definite occurrences of scrapie in sheepthat have been reliably attributed to the use of non-commercial vaccinescontaining ovine starting materials. For this reason, the issue isdiscussed below. Other forms of iatrogenic transmission of TSE have beenrestricted to humans and human tissues. For the sake of completeness andconvenience, these subjects are briefly discussed below.

III.3.1 VACCINESReference has already been made to the occurrence of at least severalhundred cases of scrapie in British sheep as a direct result of the useof a vaccine against the tick transmitted, viral disease, louping-ill(Gordon, Brownlee and Wilson, 1939, Gordon, 1946 and Greig, 1950). Thisoccurrence resulted from the accidental use of scrapie-infected sourcematerial and processing methods that did not inactivate the scrapieagent that was unknowingly present. A more recent possible occurrence ofpossible iatrogenic scrapie has recently been reported in Etna Silvercrossbred goats in Italy by Cappucchio et al., (1998). The goats werekept at grass and concentrate rations were not fed, thus eliminating asource of infection from feed via mammalian proteins. Animals over twomonths old were annually vaccinated against contagious agalactia causedby Mycoplasma agalactiae. The vaccine included central nervous systemfrom pathogen-free sheep. The mortality rate in the goats reached28% in 1 herd, 60% in the second and 5.5% in a third herd. About halfthe 56 goats were between 2.5 - 3 years old. Only 1.15% of sheep thatwere kept with the goats developed scrapie. Scrapie was confirmed bymicroscopic examination of the brain and by detection of PrPSc includingby immunocytochemistry. PrPSc was widespread in the brain and beyondsites of vacuolar change. The high mortality, severe loss of weight andsimultaneous appearance in the three herds were distinctly unusualfeatures in this outbreak. The source of infection remains uncertain andunproven but iatrogenic transmission must be considered.A larger epidemic involving 20 outbreaks of scrapie in sheep and goats,also in Italy, has been even more recently reported by Agrimi et al.,(1999). The annual incidence ranged from 1% to 90% with a mean incidencefor goats of 26% and for sheep of 10%. The total number of cases insheep and goats together was 1040. The clinical disease was confirmed bymicroscopic examination of the brain and PrP immunocytochemistry orWestern blotting. The high incidence in goats, the highwithin-flock/herd incidence, the temporal clustering, absence ofcommercial concentrate feeding in eight flocks and association with theuse of a sub-cutaneously administered M. agalactiae vaccine, preparedlocally using brain and mammary tissue from clinically healthy sheep,strongly suggests an iatrogenic origin. Scrapie appeared between 23 and35 months after the vaccine was administered. A third outbreak insouthern Italy attributed also to the same vaccine has been described byCaramelli et al, (2001) in a mixed flock of Comisana sheep and half-bredgoats in an upland area of southern Italy. High crude mortality andscrapie incidence occurred in both species and a large proportion ofaged animals were affected. The neuropathology was similar to that inother sheep in Italy with iatrogenic disease but different fromconventional natural scrapie. Affected sheep were all of the mostsusceptible genotype (Codon 171 QQ). It is stressed that the vaccinesincriminated in the transmission of scrapie in all these incidents arenot commercially produced. They have been prepared and distributedlocally within the country. Dr Subash Arya has repeatedly drawnattention to the possible risk of transmitting CJD to humans vaccinatedwith sheep-brain derived vaccines in India, e.g. Arya, (1994). However,neither Dr Arya nor any of his colleagues has yet found any such case.The episodes of scrapie resulting from the use of vaccines prepared frominfected sheep tissues emphasises the need for caution and mandatoryselection of safe sources for starting materials used in the manufactureof vaccines. Such vaccines could theoretically at least, be used incattle thus creating a potential risk, though it is most unlikely thatthey would be licensed for this purpose in Europe. Vaccines have notbeen incriminated in the transmission of BSE (Wilesmith et al., 1988,J.W.Wilesmith, personal communication). Furthermore, large numbers ofdoses of commercially produced vaccines that have used bovine startingmaterials, have been inoculated by parenteral and oral routes intocattle throughout the world and a substantial proportion have beenproduced in Europe, but no incident of BSE has been attributed to theiruse. This is important because, since there is no species barrier, anychink in the armour protecting vaccines from contamination would havebeen revealed, but none has.

III.3.2.OTHER MEDICINAL PRODUCTS DERIVED FROM TSE-SUSCEPTIBLE SPECIESAnimal sources of material used in medicinal products vary, but mostlyare derived from cattle. There is thus at least a possibility thatunless strict precautions are taken, disease could be transmitted inthis way. It cannot be ruled out that no case ever arose by this means,but it is clear that the majority did not, even at the very beginning ofthe BSE epidemic before publication of information on BSE, and beforeany legislation was in place (Wilesmith et al., 1988). The highest risktissue is bovine brain from a clinically affected animal or one in theimmediate pre-clinical phase. Posterior pituitary extract (now preparedbiosynthetically), was available and used in veterinary practice mainlyin adult female cattle at the time of parturition, to assist treatmentof retained placenta or to assist in milk let down. However, noassociation was found between its use and the occurrence of BSE(Wilesmith et al., 1988).

http://europa.eu.int/comm/food/fs/sc/ssc/out236_en.pdf

Indian J Pediatr 1991 Sep-Oct;58(5):563-5

Arya SC.

Centre for Logistical Research and Innovation, Greater Kailash, New Delhi.

BMJ 1996;313:1405 (30 November)LettersBlood donated after vaccination with rabies vaccine derived from sheepbrain cells might transmit CJDEDITOR,--Janet Morgan reports that the National Blood Authority inBritain has decided to tighten the donor screening programme to excludetransmission of Creutzfeldt-Jakob disease or its variant through blooddonations.1 Prospective donors will be prevented from donating blood ifthey have a history of treatment with human growth hormone or if one oftheir siblings, parents, or grandparents developed the disease. I wouldpoint out that similar care should also be taken when immigrants fromAsia and Africa offer to donate blood, in case they received rabiesvaccine derived from culture of sheep brain cells when they were livingin their country of origin.

In many countries in Asia and Africa limited supplies of imported rabiesvaccines derived from culture of human cells have been available. Manypeople continue to be offered indigenously produced sheep brain vaccineafter exposure to a rabid animal. Scrapie is known to exist in sheeparound many centres where the vaccine is produced. In the mountain sheepof the Kumaon foothills in the Himalayas, for example, scrapie wasestablished more than four decades ago and 1-10% of the flock wasreported to have the disease in 1961.2 In the Himalayan foothills theCentral Research Institute continues to produce four to five milliondoses of sheep brain vaccine annually. Transmission of abnormal prionprotein, PrPsc, in sheep brain vaccine might have occurred in some ofthe 30 documented cases of Creutzfeldt-Jakob disease in differentregions in India.3 Because Creutzfeldt-Jakob disease has a latency ofabout 20 years, many recipients of sheep brain rabies vaccine couldemigrate to Britain before becoming ill.

Before accepting blood donations from immigrants it would be desirableto ask the potential donors whether they were exposed to a rabid animaland immunised with sheep brain rabies vaccine in their country oforigin. Furthermore, indirect assessment should be possible through, forexample, assay looking for antibodies specific to rabies.

Clinical microbiologist Centre for Logistical Research and Innovation,M-122 (of part 2), Greater Kailash-II, New Delhi-110048, India

Thirty cases including 20 definite and 10 probable cases ofCreutzfeldt-Jakob disease (CJD) seen in India between 1971 and 1990 arereported. Demographic analysis has shown similarities to the previouslypublished reports from other parts of the world. Though 21 (70%) ofcases were from two centers--Bombay and Bangalore-, suggestingclustering, this seems to be more apparent than real. One subject workedin the medical field, where possibility of iatrogenic transmission couldnot be ruled out. None of the cases had positive family history of CJD.There is no epidemiological data of CJD from India so far and hence thisreport is one such pilot study.

i recieved the 1947 report of the Louping-ill vaccineincident and posted on www here;

Louping-ill vaccine (scrapie transmission by vaccine)

THE VETERINARY RECORD516 No 47. Vol. 58November 23rd, 1946

NATIONAL VETERINARY MEDICAL ASSOCIATION OF GREAT BRITAIN AND IRELAND

ANNUAL CONGRESS, 1946

snip...

The enquiry made the position clear. Scrapie was developing inthe sheep vaccinated in 1935 and it was only in a few instancesthat the owner was associating the occurrence with louping-illvaccination. The disease was affecting all breeds and it wasconfined to the animals vaccinated with batch 2. This was clearlydemonstrated on a number of farms on which batch 1 had beenused to inoculate the hoggs in 1935 and batch 2 to inoculatethe ewes. None of the hoggs, which at this time were three-year-old ewes. At this time it was difficult to forecast whether allof the 18,000 sheep which had received batch 2 vaccine woulddevelop scrapie. It was fortunate, however, that the majority ofthe sheep vaccinated with batch 2 were ewes and therfore allthat were four years old and upwards at the time of vaccinationhad already been disposed of and there only remained the eweswhich had been two to three years old at the time of vaccination,consequently no accurate assessment of the incidence of scrapiecould be made. On a few farms, however, where vaccination wasconfined to hoggs, the incidence ranged from 1 percent, to 35 percent,with an average of about 5 percent. Since batch 2 vaccinehad been incriminated as a probable source of scrapie infection,an attempt was made to trace the origin of the 112 sheep whosetissues had been included in the vaccine. It was found that theyhad been supplied by three owners and that all were of theBlackface or Greyface breed with the exception of eight whichwere Cheviot lambs born in 1935 from ewes which had been incontact with scrapie infection. Some of these contact ewesdeveloped scrapie in 1936-37 and three surviving fellow lambs tothe eight included in the batch 2 vaccine of 1935 developedscrapie, one in September, 1936, one in February, 1937, and onein November, 1937. There was, therefore, strong presumptiveevidence that the eight Cheviot lambs included in the vaccinealthought apparently healthy were, in fact, in the incubative stageof a scrapie infection and that in their tissues there was aninfective agent which had contaminated the batch 2 vaccine,rendering it liable to set up scrapie. If that assumption wascorrect then the evidence indicated that:-

(1) the infective agent of scrapie was present in the brain, spinalcord and or spleen of infected sheep:(2) it could withstand a concentration of formalin of 0-35 percent,which inactivated the virus of louping-ill:(3) it could be transmitted by subcutaneous inoculation;(4) it had an incubative period of two years and longer.

Two Frenchmen, Cuille & Chelle (1939) as the result of experimentscommenced in 1932, reported the successful infection ofsheep by inoculation of emulsions of spinal cord or brain materialby the intracerebral, epidural, intraocular and subcutaneous routesThe incubation period varied according to the route employed,being one year intracerebrally, 15 months intraocularly and 20months subcutaneously. They failed to infect rabbits but succeededin infecting goats. Another important part of their workshowed that the infective agent could pass throught a chamberland1.3 filter, thus demonstrating that the infective agent was afiltrable virus. It was a curious coincidence that while theywere doing their transmission experiments their work was beingconfirmed by the unforeseeable infectivity of a formalinized tissuevaccine.

As a result of this experience a large-scale transmision experimentinvolving the ue of 788 sheep was commenced in 1938 on afarm specially taken for the purpose by the Animal DiseasesResearch Association with funds provided by the AgriculturalResearch Council. The experiment was designed to determine thenature of the infective agent and the pathogenesis of the disease.It is only possible here to give a summary of the result whichshowed that (1) saline suspensions of brain and spinal cord tissueof sheep affected with scrapie were infective to normal sheepwhen inoculatted intracerebrally or subcutaneously; (2) the incubationperiod after intracerebral inoculation was seven months andupwards and only 60 percent of the inoculated sheep developedscrapie during a period of four and a half years; (3) the incubationperiod after subcutaneous inoculation was 15 months and upwardsand only about 30 percent of the inoculated sheep developedthe disease during the four and a half years: (4) the infectiveagent was of small size and probably a filtrable virus.

The prolonged incubative period of the disease and the remarkableresistance of the causal agent to formalin are features ofdistinct interest. It still remains to determine if a biological testcan be devised to detect infected animals so that they can bekilled for food before they develop clinical symptoms and toexplore the possibilities of producing an immunity to the disease...snip...END

In the 1984 census of sheep carried out in India - at least 20% of the flock were contaminated with Scrapie. Indians, those who eat this meat, eat the brains of the animals too - as a delicacy. Besides, in India, the rabies vaccine is "grown" on the sheep's brain, from where it is extracted and given to you as a vaccine.

Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.